ZrO2-β-cyclodextrin catalyzed synthesis of 2,4,5-trisubstituted imidazoles and 1,2-disubstituted benzimidazoles under solvent free conditions and evaluation of their antibacterial study

Article abstract of DOI:10.1039/c5ra13891d

A series of 2,4,5-trisubstituted imidazoles and 1,2-disubstituted benzimidazoles catalyzed by ZrO₂-supported-β-cyclodextrin (ZrO₂-β-CD) under solvent free conditions have been synthesized and characterized by spectral methods. The nanoparticles (ZrO₂-β-CD), prepared by a simple one-pot-coprecipitation method and were characterized by PXRD, SEM, and TEM techniques. The nano (ZrO₂-β-CD) particles were found to be an effective heterogeneous reusable catalyst for the effective synthesis of imidazoles and benzimidazoles under solvent free conditions and all of the synthesized derivatives were evaluated for their antibacterial activity against six bacterial strains.

Full text of DOI:10.1039/c5ra13891d

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Sharath kumar, K. N. Thimmaiah, K. S. Rangappa and S. shashikanth, RSC Adv., 2015, DOI:
10.1039/C5RA13891D.
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ZrO2ꢀβꢀcyclodextrin catalyzed synthesis of 2,4,5ꢀtrisubstituted imidazoles and 1,2ꢀ
disubstituted benzimidazoles under solvent free conditions and evaluation of their
antibacterial study
Yarabhally R.Girish,a Kothanahally S. Sharath Kumar,a Kuntebommanahalli N. Thimmaiah,b
Kanchugarakoppal S. Rangappa,a* and Sheena Shashikanth,a*
aDepartment of Studies in Chemistry, Manasagangotri, University of Mysore, Mysoreꢀ570006.
bDepartment of Chemistry, Northwest Mississippi Community College/University of Mississippi,
DeSoto Center, Southaven, Mississippiꢀ38671, USA.
*Corresponding author.
Tel. No.: +91ꢀ821ꢀ2419668
Eꢀmail: shashis1956@gmail.com
Abstract
A series of 2,4,5ꢀtrisubstituted imidazoles and 1,2ꢀdisubstituted benzimidazoles catalyzed by
ZrO2ꢀsupportedꢀβꢀcyclodextrin (ZrO2ꢀβꢀCD) under solvent free conditions have been
synthesized and characterized by spectral methods. The nanoparticles (ZrO2ꢀβꢀCD), prepared by
a simple oneꢀpotꢀcoprecipitation method and were characterized by PXRD, SEM, and TEM
techniques. The nano (ZrO2ꢀβꢀCD) particles were found to be an effective heterogeneous
reusable catalyst for the effective synthesis of imidazoles and benzimidazoles under solvent free
conditions and all of the synthesized derivatives were evaluated for their antibacterial activity
against six bacterial strains.
Keywords: Imidazoles, Benzimidazoles, Condensation, Regioselective, ZrO2 supported ꢀβꢀ
cyclodextrin nanoparticles (ZrO2ꢀβꢀCD).

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Introduction
Imidazoles, an important class of five membered nitrogen containing heterocycles, play a vital
role in the synthesis of biologically active molecules. These compounds are known to possess
diverse biological applications as inhibitors of transforming growth factorꢀβ type I receptor
(ALK5), mGAT3 selective GABA uptake inhibitors, antiꢀinflammatory agents, antiꢀcancer
agents, fungicides, antithrombotic agents, antiꢀalzheimer's agents, and for the determination of
propyl gallate in edible oil.1 These compounds also play an important role as parent πꢀ
conjugated backbone for organic chromophores for intramolecular chargeꢀtransfer process,2 for
enhanced charge transfer for heteroꢀjunction solar cell applications,3 and as a new building block
for blue light emitting materials.4 Imidazoleꢀbased heterocycles have also been used for
energetic materials.5 In addition phosphino imidazoles and imidazolium salts have been used for
the synthesis of Suzuki C–C coupling reactions.6
Benzimidazole derivatives have drawn considerable attention due to their widespread biological
applications such as antitumor,7 antimicrobial,8 antiꢀinflammatory,9 antihelminthic10 activities. In
addition, benzimidazoles are important intermediates in various organic reactions.11ꢀ13 Therefore,
the synthesis of benzimidazoles has gained much importance in recent years. Several synthetic
efforts have been made for the synthesis of benzimidazoles using various catalysts.14ꢀ21
The conventional methods for the synthesis of 2,4,5ꢀ trisubstituted imidazoles are mainly based
on the cyclo condensation of a 1,2ꢀdiketone with an aldehyde using ammonium acetate as the
nitrogen source.22 Various catalysts under different reaction conditions have been employed for
the synthesis of imidazole based derivatives.23 Most of the reported methods suffer from one or
the other serious drawbacks such as high reaction temperature, long duration, use of toxic and
expensive chemicals as starting materials, use of moistureꢀsensitive catalysts and formation of

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byproducts. Recently Nanoparticles have been extensively used in the field of medicinal
chemistry,24,25 heterocyclic chemistry,26,27 as sensors for detection of hydrazine,28 optoelectronic
materials,29 in enhancing the upꢀconversion luminescence,30 and as electron transfer mediators in
a bioꢀelectrochemical systems.31,32
Cyclodextrins (CDs) are natural oligosaccharides linked by αꢀ1,4ꢀglycosidic linkage, having
hydrophobic cavities inside and hydrophilic outside. The substrates can be entrapped in the
hydrophobic cavity of the cyclodextrin felicitating the catalysis of the chemical reactions for
higher selectivity. βꢀcyclodextrins have been extensively used in various biochemical
applications such as for drug and gene delivery,33 to detect micromolar quantities of Pb2+ in
aqueous solution,34 for removing diazepam from blood,35 for optical sensing and chiroselective
sensing of different substrates using a fluorescence resonance energy transfer (FRET).36 In
addition, βꢀcyclodextrin has also been used as catalyst for the synthesis of various hetrocycles.37
In recent years ZrO2 nanoparticles have gained much attention in catalysis due to their specific
amphoteric properties, excellent mechanical strength and stiffness, high thermal stability and
dielectric properties.38ꢀ40 ZrO2 can exist in three polymorphic forms depending on the
temperature range namely monoclinic (room temperature–1172 °C), tetragonal (1172–2347 °C)
and cubic (above 2347 °C).41,42 ZrO2 have found wide spread applications in the field of science
and technology.43ꢀ54
In continuation of our efforts in nanoparticles catalyzed synthesis of diverse nitrogen containing
heterocycles,55 we have described ZrO2ꢀβꢀCD catalyzed synthesis of imidazoles and 1,2ꢀ
disubstituted benzimidazoles from readily available benzyl, 1,2ꢀphenylenediamine, aldehydes
and ammonium acetate under solvent free conditions (Scheme 1) using ZrO2ꢀβꢀCD as an

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environment friendly and reusable heterogeneous catalyst (Scheme 1). It is noteꢀworthy to
mention that, ZrO2ꢀsupported βꢀcyclodextrin nanoparticles have never been used in the field of
synthetic organic chemistry for the synthesis of any heterocycles.
Scheme 1 Synthesis of 2,4,5ꢀtrisubstituted imidazoles by multiꢀcomponent reaction of benzil,
aldehydes, NH4OAc, and synthesis of 1,2ꢀdisubstituted benzimidazoles using 1,2ꢀdiamine and
aldehyde in the presence of ZrO2 supported ꢀβꢀcyclodextrin catalyst under solventꢀfree
conditions.
Results and Discussion
The ZrO2 nanoparticlesꢀsupported βꢀcyclodextrin nanoparticles (ZrO2ꢀβꢀCD) was prepared by a
simple oneꢀpot coꢀprecipitation method by using ZrOCl2.8H2O, and NH4OH (Scheme 2). 56 The
morphology of the prepared ZrO2ꢀβꢀCD nanoparticles were characterized by ATRꢀIR, PXRD,
SEM, TEM and EDAX analysis, which confirmed the successful preparation of the ZrO2 ꢀ
supported βꢀcyclodextrin nanoparticles.

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Fig. 1 shows the ATRꢀIR spectrum of ZrO2 ꢀβꢀcyclodextrin nanoparticles. The bands observed at
844 and 510 cmꢀ1, which is due to asymmetric and symmetric stretching modes of ZrO2. The
broad band appears at 3337 cm−1 is for hydroxyl stretching vibration of βꢀcyclodextrin. The peak
at 1348 corresponds to CꢀC stretching vibrations of βꢀcyclodextrin. The peak observed at 1561
cm−1 may be assigned to the bending vibrations of water molecules trapped into the ZrO2 nano
particles
Fig. 1 ATRꢀIR spectrum of the ZrO2ꢀ supported ꢀβꢀcyclodextrin
Scheme 2: Preparation of ZrO2ꢀβꢀCD nanoparticles

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The XRD analysis of ZrO2 and ZrO2 supported ꢀβꢀcyclodextrin nanoparticles indicate five
characteristic peaks at 2θ = 30.2°, 35.15°, 50.44°, 60.14°, and 62.98° corresponding to (111),
(200), (220), (311), and (331) planes, respectively as shown in Fig.2. All diffraction peaks and
positions match with those from the JCPDS card (Joint Committee on Powder Diffraction
Standards no. 37ꢀ1484) calculated from the Scherer’s equation.
where d is the average grain size of the crystallites, λ the incident wavelength, θ, the Bragg angle
and β the diffracted fullꢀwidth at halfꢀmaximum (FWHM) in radians caused by the crystallites.
The values obtained using the above equation for the ZrO2 and ZrO2 supported ꢀβꢀcyclodextrin
nanoparticles were 20 and 1.20 nm, respectively. This reveals that the ZrO2ꢀβꢀCD nanoparticles
are evenly distributed throughout the specimen, which assists in reducing the size of the
nanoparticles.
2500
350
300
250
200
150
100
50
(111)
b)
2000
1500
1000
500
0
a)
(111)
(220)
(311)
(331)
(200)
0
0
10
20
30
40
50
60
70
80
90
20
40
60
80
2Θ (deg)
2Θ
(deg)
Fig. 2 (a) XRD pattern of the ZrO2; (b) XRD pattern of the ZrO2ꢀ supported ꢀβꢀcyclodextrin

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The SEM and TEM of the prepared ZrO2ꢀβꢀCD nanoparticles were shown in Fig. 3. The TEM
image of the catalyst shows that nano particles are highly aggregated. The average size of these
particles is about 1ꢀ2 nm, which shows a close agreement with the values calculated by XRD
data. The SEM image of the supported catalyst confirms that these nanoparticles are unevenꢀ
sized particles due to deposition of βꢀcyclodextrin complex nanoparticles on the surface of ZrO2
and most of them are almost spherical in shape.
Fig. 3 (a) SEM image of ZrO2 supported ꢀβꢀcyclodextrin; (b) TEM image of ZrO2 supported ꢀβꢀ
cyclodextrin.
The At % peaks of the elements were found to be C (39.15 %), O ( 25.04%) and Zr (35.81%) in
the EDAX spectrum of ZrO2ꢀβꢀCD nanoparticles as shown in Fig.4.

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Fig. 4 EDAX spectrum of ZrO2 supported ꢀβꢀcyclodextrin.
To optimize the reaction conditions for the synthesis of 2,4,5ꢀtrisubstituted imidazoles,
benzaldehyde, benzil and ammonium acetate were used as model substrates and the reaction was
screened in different solvents, temperatures, and various amounts of catalyst and the results are
summarized in Table 1. In the presence of βꢀCD and water as solvent at 80 ºC, reaction yielded
the desired product 3a in 30% yield (Table 1, entry 1), the low yield may be due to the partial
missicibility of benzil and aldehyde in aqueous solvent at 80 °C. Next, a series of catalysts were
examined, among them ZrO2ꢀβꢀCD was found to be better catalyst for the formation of 3a with
65% yield in presence of water as solvent at 100 ºC (Table 1, entry 5). We next examined the
reaction in presence of various solvents and solvent free conditions (Table 1, entries 6ꢀ16). In the
presence of solvents the reaction produced the product 3a in low yields (Table 1 entries 1ꢀ8) and
under solvent free condition the reaction underwent smoothly and gave the desired product in
good yield (Table 1 entries 9ꢀ15). Initially 20 mol% ZrO2ꢀβꢀCD at 100 ºC, gave the desired

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product in very low yield (Table 1, entry 11). When the catalyst load was increased from 20 to
40 mol %, it resulted in increase in yield of 3a up to 96% and the reaction was completed in just
40 minutes at 100 ºC (Table 1, entry 13).
Table 1: Condensation of benzil, benzaldehyde, and ammonium acetate using different catalysts
and solvents
Catalyst Nitrogen
Entry Catalyst
loading
(mol %)
40
source
solvent Temp (°C) Time (h) Yield (%)b
1
βꢀCD
NH4OAc water
NH4OAc Water
NH4OAc water
NH4OAc Water
NH4OAc Water
NH4OAc DMF
NH4OAc DMF
NH4OAc EtOH
NH4OAc Neat
NH4OAc Neat
NH4OAc Neat
NH4OAc Neat
NH4OAc Neat
NH4OAc Neat
NH4OAc Neat
80
80
7
6
6
6
4
8
4
3
2
1
1.3
4
0.4
4
30
40
60
50
65
55
60
60
40
50
50
70
96
70
60
ꢀꢀꢀꢀ
2
ZrO2ꢀCu2(II)ꢀβꢀCD 40
3
4
5
ZrO2ꢀAl2O3
ZrO2ꢀβꢀCD
ZrO2ꢀβꢀCD
40
10
20
100
100
100
100
100
100
100
100
100
100
100
100
100
100
6
ZrO2ꢀCu2(II)ꢀβꢀCD 40
7
8
9
ZrO2ꢀβꢀCD
ZrO2ꢀβꢀCD
βꢀCD
40
40
40
40
20
20
40
10
11
12
13
14
15
16
ZrO2ꢀAl2O3
ZrO2ꢀβꢀCD
ZrO2ꢀCu2ꢀβꢀCD
ZrO2ꢀβꢀCD
ZrO2ꢀCu2(II)ꢀβꢀCD 40
ZrO2ꢀAl2O3
ZrO2ꢀβꢀCD
40
40
0.5
3
NH4Cl
Neat
a Reaction conditions: benzil (1.0 mmol), benzaldehyde (1.0 mmol), NH4OAc (2.0 mmol),
catalyst and solvent (10 mL), or neat. b Isolated yield.
With the optimized reaction condition in hand, we next explored the generality and scope of the
protocol using various aldehydes and keeping 1,2ꢀdiketone same for the synthesis of 2,4,5ꢀ
trisubstituted imidazoles. The results are shown in Tables 2. These results show that the reactions
are equally facile with both electronꢀdonating and electronꢀwithdrawing substituent’s present on

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the aromatic aldehydes resulting in high yields of the desired imidazoles. The known products
were characterized by comparing their physical properties with those reported in the literature.
Table 2 : Solvent free synthesis of 2,4,5ꢀtrisubstituted imidazoles catalyzed by ZrO2ꢀβꢀCD
Entry
1
Diketone
R
Product
Time(h) Yieldb,c(%)
0.40
9657
3a
2a
1
1
0.40
8557
2
3
2b
3b
1
1
0.50
8658
2c
3c
0.50
0.50
8758
4
5
2d
3d
1
8958
3e
2e

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1
0.35
0.45
9258
6
2f
CHO
3f
1
1
9058
7
8
3g
2g
2h
Cl
Ph
Ph
N
0.50
0.45
9758
N
H
3h
9
8958
1
3i
3j
2i
0.35
9759
1
1
1
10
2j
0.35
0.40
96
11
12
2k
3k
3l
8060
2l
13
1
0.45
94

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2m
2n
3m
14
1
0.55
98
3n
a Reaction conditions: 1,2ꢀdiketone (1.0 mmol), aldehyde (1.0 mmol), NH4OAc (2.0 mmol),
ZrO2ꢀβꢀCD (40 mol %), neat. b Isolated yield.C Literature reported compounds.
We next explored the generality of this protocol for the synthesis of 1,2ꢀdisubstitited
benzimidazoles. Initially, benzaldehyde and 1,2ꢀphenylenediamine were selected as model
substrates for the synthesis of 1,2ꢀdisubstituted benzimidazoles and the results are presented in
Table 3. The reaction in presence of ZrO2ꢀβꢀCD in EtOH as solvent at room temperature gave
desired 1ꢀbenzylꢀ2ꢀphenylꢀ1Hꢀbenzo[d]imidazole 5a in 55% yield (Table 3, entry 1). We next
examined the reaction using different catalysts such as ZrO2ꢀβꢀCD, Nano TiO2, Nano CuO,
Mo/ZrO2, ZnOꢀAl2O3, βꢀCD, ZrO2ꢀAl2O3 and ZrO2ꢀCu2ꢀβꢀCD (Table 3, entries 1ꢀ11). Among
them ZrO2ꢀβꢀCD was found to be better catalyst for the synthesis of 1,2ꢀdisubstituted
benzimidazoles. We next converged our interest to study the effect of solvents on the product
yield. Among various solvent screened, DMF was found to be better and gave the desired
product 5a in 85% yield at 100°C (Table 3, entry 4). Then the reaction was performed using
ZrO2ꢀβꢀCD as catalyst by varying temperature and mol% of catalyst under solvent free condition.
Initially 20 mol% of ZrO2ꢀβꢀCD at 100 ºC gave only 85% of yield even after 1.3h (Table 3,
entry 13). Then the reaction was screened by increase in catalyst load from 20 to 40 mol %
which gave increase in yield up to 95% (Table 3, entry 14).

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Table 3: Condensation of benzil, benzaldehyde, and ammonium acetate using different catalysts
and solvents
Entry
Catalyst
Mol (%) Solvent Temp(ºC) Time (h)
yieldb
1
2
3
4
5
6
7
8
ZrO2ꢀβꢀCD
ZrO2ꢀβꢀCD
ZrO2ꢀβꢀCD
ZrO2ꢀβꢀCD
Nano TiO2
Nano CuO
Mo/ZrO2
ZnOꢀAl2O3
βꢀCD
ZrO2ꢀAl2O3
40
40
40
40
40
40
40
40
40
40
EtOH
H2O
Rt
Rt
12
18
2
3
8
12
18
5
12
8
55
60
70
85
55
45
60
50
70
60
80
70
85
95
75
40
60
50
EtOH
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
neat
neat
neat
neat
neat
neat
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
9
10
11
12
13
14
15
16
17
18
ZrO2ꢀCu2ꢀβꢀCD 40
5
ZrO2ꢀβꢀCD
ZrO2ꢀβꢀCD
ZrO2ꢀβꢀCD
Nano TiO2
Nano CuO
βꢀCD
10
20
40
40
40
40
40
2.3
1.3
1
1.15
2.15
1.3
2
ZnOꢀAl2O3
neat
a Reaction conditions: 1,2ꢀphenylenediamine (1.0 mmol), benzaldehyde (2.0 mmol), catalyst and
solvent (10 mL), or neat. b Isolated yield, rt = room temperature
After optimization of the reaction condition, different aldehydes and 1,2ꢀphenylenediamine were
used as substrates for the synthesis 1,2ꢀdisubstituted benzimidazoles, and the results are shown in
Tables 4. Reaction underwent comparatively fast when electronꢀdonating substituent’s such as
methyl, methoxy, ethyl, or propyl group were present on the substrates. Whereas, the electronꢀ
withdrawing substituent’s such as CF3, F, Br, Cl, NO2 took more time for completion of reaction.
Structures of the newly synthesized compounds were characterized by spectroscopic and

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elemental analysis data. The known products were characterized by comparing their physical
properties with those reported in the literature.
Table 4: Solvent free synthesis of 1,2ꢀdisubstituted benzimidazoles catalyzed by ZrO2ꢀβꢀCD
Entry
15
Diamine
Aldehyde
Product
Time (h) Yield b,c(%)
1.00
9314
2a
4
4
5a
5b
16
17
1.00
1.50
8514
2f
4
4
9515
2c
5c
18
1.30
8716
5d
2d

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CHO
4
19
20
1.45
1.30
9216
2e
5e
9617
4
4
2b
5f
21
22
2.00
1.40
8018
2g
2h
5g
4
9319
5h
23
24
4
4
1.45
1.40
88
90
2i
5i
5j
2j

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4
25
1.35
90
5k
2k
a Reaction conditions: and 1,2ꢀphenylenediamine (1.0 mmol), aldehyde (2.0 mmol), ZrO2ꢀβꢀCD
(40 mol %) neat. b Isolated yield. cLiterature reported compounds.
Since many nitrogen containing heterocyclic derivatives61 possess wide range of biological
activities we have screened all the synthesized derivatives for their antibacterial activity. The
antibacterial activity of the synthesized test samples 3(aꢀn) and 5(aꢀk) were screened for their
antibacterial activity against both Gramꢀpositive and Gramꢀnegative bacterial strains, using
previous reported procedure.62 The results shown in Table 5 indicates that these compounds
exhibit a variable zone of inhibition ranging from 4ꢀ32 mm. These compounds shown moderate
antibacterial activity against gramꢀpositive bacteria Bacillus subtilis (MTCC 121), with inhibition
zone around <19 mm except for the compounds 3b, 3c, 3n, 5a, 5c, 5eꢀj, which do not show any
antibacterial activity. In contrast compounds 3aꢀ3n, 5aꢀ5c and 5gꢀ 5j did not inhibit the growth of
Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter aeruginosa, Shigella flexneri
(except compounds 3f, 3g, 3h in Pseudomonas aeruginosa) even at maximum concentration of
10 µg per disc. However the compound 5f showed very good inhibition to the growth of
Klebsiella pneumonia and Enterobacter aeruginosa with inhibition value of 32 and 26 mm
respectively.

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Table 5 Antimicrobial activity of of the synthesized compounds 3(aꢀn) and 5(aꢀk).
Zone of inhibitiona (mm), dose (5 ꢁg, 10 ꢁg per disc)
Comp
3a
R
C6H5
ꢁg per disc K.pb
B.sc
5
13
ꢀ
ꢀ
ꢀ
ꢀ
5
13
8
18
9
18
9
18
8
19
7
15
8
17
5
13
5
11
6
13
ꢀ
P.ad
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
10
ꢀ
ꢀ
ꢀ
E.ae S.ff
S.tg
5
10
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
10
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
10
ꢀ
5
10
5
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
8
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
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4ꢀEtC6H4
3b
3c
3d
3e
3f
10
5
10
5
4ꢀCF3C6H4
C7H5O2
10
5
10
5
4ꢀFC6H4
ꢀ
4ꢀOMeC6H4
4ꢀMeC6H4
2ꢀClC6H4
5
12
6
13
6
15
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
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10
10
5
10
5
3g
3h
3i
10
5
10
5
3ꢀNO2C6H4
3,4ꢀdiOMeC6H3
2,3ꢀdiOMeC6H3
3ꢀBrC6H4
3j
10
5
10
5
3k
3l
10
5
10
5
3ꢀFC6H4
ꢀ
ꢀ
ꢀ
3m
3n
4ꢀPropC6H4
10
5
10
5
10
5
10
5
10
5
10
5
10
5
ꢀ
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7
14
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20
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5
12
8
13
4
12
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6
10
7
12
ꢀ
ꢀ
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18
7
15
7
15
6
14
5
11
4
13
8
C6H5
5a
5b
5c
5d
5e
5f
2ꢀClC6H4
4ꢀFC6H4
4ꢀOMeC6H4
4ꢀMeC6H4
C7H5O2
ꢀ
ꢀ
ꢀ
ꢀ
10
15
8
13
15
32
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13
26
14
26
13
26
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3ꢀNO2C6H4
5g
10
ꢀ
ꢀ
17
ꢀ
9
16

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DOI: 10.1039/C5RA13891D
3ꢀBrC6H4
3ꢀFC6H4
5
10
5
ꢀ
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5h
5i
10
5
10
5
10
10
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5
10
22
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8
15
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24
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8
16
5
12
20
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13
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9
17
4ꢀEtC6H4
4ꢀPropC6H4
5j
5k
Streptomycin
aThe values indicate the average diameters in mm (of two trials) for the zone of growth inhibition
observed after 24 h of incubation at 37 °C. Klebsiella pneumoniae MTCC 7407; cBacillus
b
subtilis MTCC 121; dPseudomonas aeruginosa ꢀ MTCC 7903; eEnterobacter aeruginosa MTCC
7325; Shigella flexneri MTCC 1457; gSalmonella typhi MTCC 733.
f
Conclusion
In conclusion, we have developed an efficient and safe protocols for the synthesis of 2,4,5ꢀ
trisubstituted imidazoles and 1,2ꢀdisubstituted benzimidazoles under solvent free conditions.
More efficient nanoparticleꢀcatalyst ZrO2 supported ꢀβꢀcyclodextrin (1–5 nm range) was easily
prepared by coꢀprecipitation method. The analysis data reveal that the nano ZrO2 supported ꢀβꢀ
cyclodextrin was an effective heterogeneous reusable catalyst for the synthesis of 2,4,5ꢀ
trisubstituted imidazoles and 1,2ꢀdisubstituted benzimidazoles under solventꢀfree mild
conditions. Further the compounds have been screened for the antibacterial activity. Compound
5f at 10ꢁg per disc showed potent inhibitory activity against K.pneumoniae, compared to the
standard (Streptomycin 10ꢁg per disc) at the same concentration. None the less, further studies
needed to be conducted for molecular mechanism of 5f derivatives against the human pathogen
K.pneumonia. The present study revealed the potential application and development of synthetic
novel molecules against human pathogen and it also proposed for some more studies relating to
antimicrobial during further studies.

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DOI: 10.1039/C5RA13891D
Experimental Section
General Methods
Zirconium oxychloride (ZrOCl2.8H2O, >99.0%), ammonia (NH3.H2O, 25%) was purchased
from s.d. FineꢀChem Ltd., India. βꢀcyclodextrin was purchased from SigmaꢀAldrich India.
Deionized water was used for all workup procedures. Melting points were measured on secor
1
13
INDIA apparatus and are uncorrected. H NMR and C NMR were recorded on VNMRSꢀ400
(Agilent Technologies) NMR spectrometer in CDCl3. Tetramethylsilane (TMS; δ = 0.00 ppm)
served as internal standard. The corresponding residual nonꢀdeuterated solvent signal (CDCl3: δ
= 77.00 ppm) was used as internal standard for 13C NMR. Performed column chromatography on
silica gel 60ꢀ120 mesh (Merck). Unless otherwise noted, materials obtained from commercial
suppliers were used without further purification. Mass spectra were measured with Micromass
QꢀTof (HRESIꢀMS). DMF was dried over CaH2 for 2 h and filtered. The catalyst was
characterized by ATRꢀFourier transform infrared (ATRꢀIR) spectra, recorded using a Thermoꢀ
Nicolet FTIR spectrometer (Model 5700, Madison, WI) fitted with a single bounce attenuated
total reflectance (ATR) accessory with a ZnSe crystal of range 400ꢀ4000 cmꢀ1. Xꢀray powder
diffraction (PXRD) was carried out on a XRD 7000, Shimandzu diffractometer with CuKα
radiation. Scanning electron microscopy (SEM) images were obtained using a JEOL JXAꢀ8530F
microscope. Transmission electron microscopy (TEM) images were performed on PHILIPS
CM200 electron microscope at an acceleration voltage of 20ꢀ200kV. TGA thermograms of the
nanoparticles were obtained under nitrogen on a Perkin–Elmer TGA 7 analyzer at a heating rate
of 20°C minꢀ1.

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Preparation of ZrO2ꢀsupported ꢀβꢀcyclodextrin nanoparticles
The ZrO2ꢀsupported ꢀβꢀcyclodextrin nanoparticles were prepared by a chemical coꢀprecipitation
method.25 2.42 g of zirconium oxychloride (ZrOCl2.8H2O) and 1.04 g of ꢀβꢀcyclodextrin were
dissolved in 50 mL of deionized water under intense stirring at 90°C. Subsequently, ammonia
(25%) was added drop wise to the reaction mixture with stirring. The nanoparticles formed were
collected by filtration, washed with distilled water repeatedly, and dried for 24 h at room
temperature in a high vacuum.
General procedure for the synthesis of 2,4,5ꢀtrisubstituted imidazole derivatives or 2,5ꢀ
disubstituted benzimidazole derivatives in the presence of ZrO2 supported ꢀβꢀcyclodextrin
nanoparticles as catalyst under solvent free conditions.
To a mixture, of benzil (1 mmol), benzaldehyde (1 mmol), and NH4OAc (2 mmol) for 2,4,5ꢀ
trisubstituted imidazole derivatives or to a mixture of oꢀphenylenediamine (1 mmol) and
aldehyde (2 mmol) for 1,2ꢀdisubsubstituted benzimidazole derivatives, was added ZrO2ꢀβꢀCd
º
(40 mol %). The resulting mixture was heated at 100 C on an oil bath under neat conditions for
appropriate time till the completion of the reaction. After completion of reaction, as monitored
by TLC (eluent: petroleum ether: ethyl acetate: 7:3), the reaction was cooled to room
temperature. The solid thus formed was dissolved in acetone and the catalyst separated by
filtration. The mixture was concentrated on a rotary evaporator under reduced pressure and the
product obtained was washed with water and recrystallized from acetone–water 9 : 1 (v/v) to
offer the pure 2,4,5ꢀtrisubstituted imidazole derivatives.
Reusability studies
Recovery of the nanoꢀ ZrO2 supported ꢀβꢀcyclodextrin catalyst was easy and efficient. When the
reaction was complete, the precipitated products were dissolved by acetone and nanoꢀ ZrO2

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supported ꢀβꢀcyclodextrin was separated by centrifugation followed by decantation (ethanol, 5
ml). The isolated solid phase (nanoꢀ ZrO2 supported ꢀβꢀcyclodextrin) was then dried under
reduced pressure and reused for four runs without any appreciable loss in the product yield and
its catalytic activity. The same results were obtained for the catalyst recovery in condensation of
oꢀphenylenediamine (1mmol) and benzaldehyde (2 mmol) for synthesis of the corresponding
1,2ꢀdisubstituted benzimidazole under solventꢀfree conditions. Therefore, the methodologies are
environmentally friendly, cost effective and industrially important because of the catalyst reuse
and the use of safe reaction media.
Acknowledgements
YRG is thankful to UGCꢀBSR for meritorious fellowship Order no. DVꢀ5/662/RFSMS/2012–13,
New Delhi, India for financial support and we are also thankful to IOE, University of Mysore
and NCBS, Bengaluru, Karnataka, India for their support in carrying out research work regarding
the single crystal XRD and TEM analysis.
References:
1. (a) C. Guo, C. Zhang, X. Li, W. Li, Z. Xu, L. Bao, Y. Ding, L. Wang, S. Li, Bioorganic &
Medicinal Chemistry Letters., 2013, 23, 5850ꢀ5854; (b) S. Hack, B. Wörlein, G. Höfner, J.
Pabel , K. T. Wanner, European Journal of Medicinal Chemistry., 2011, 46, 1483ꢀ1498; (c)
J. G. Lombardino, E. H. Wiseman, Journal of Medicinal Chemistry., 1974, 17,1182ꢀ1188; (d)
X. Q. Wang, L. X. Liu, Y. Li, C. J. Sun, W. Chen, L. Li, H. B. Zhang, X. D. Yang, European
Journal of Medicinal Chemistry., 2013, 62, 111ꢀ121; (e) M. Mccann, R. Curran, M. Benꢀ
Shoshan, V. McKee, M. Devereux, K. Kavanagh, A. Kellett, Polyhedron., 2013, 56, 180–
188; (f) H . Nabata, M. Uchino, A. Okazaki, T.Yamazaki, K. Sakai, Japan. J. Pharmacol.,
1987, 44, 93ꢀ96; (g) J. Liu, J .Qiu, M .Wang, L .Wang, L. Su, J .Gao, Q .Gu, J .Xu, S. L
Huang, L. Q. Gu, Z. S. Huang, D. Li, Biochimica et Biophysica Acta., 2014, 1840, 2886–
2903;(h) J .Kang, L .Han, Z. Chen, J .Shen, J .Nan, Y .Zhang, Food Chemistry., 2014, 159,
445–450.
2. J. Kulhánek, F .Bureš, Beilstein J. Org. Chem., 2012, 8, 25–49.
3. C .YaoꢀTe, H .SoꢀLin, C .GuanꢀYu, S .MingꢀHsin, A. S .Thounaojam, D .Eric WeiꢀGuang,
and W. KungꢀHwa, Adv. Funct. Mater., 2008, 18, 2356–2365.
4. W .Zhiming, L .Ping, C .Shuming, G .Zhao, S .Fangzhong, Z .Wensi, X .Yuanxiang, K. W.
Hoi Sing and M. Yuguang . J.Mater. Chem., 2011, 21, 5451–5456.
5. Y. Zijun and R. B. Elliot J. Phys. Chem. A.; 2013, 117, 1756−1764.

RSC Advances
Page 22 of 25
View Article Online
DOI: 10.1039/C5RA13891D
6. B. Milde, D. Schaarschmidt, T .Rüffer, H .Lang, Dalton Trans., 2012, 41, 5377ꢀ5390.
7. W. A. Denny, G. W. Rewcastle and B. C. Baguley, J. Med. Chem., 1990, 33, 814.
8. T. Fonseca, B. Gigante and T. L. Gilchrist, Tetrahedron., 2001, 57, 1793.
9. R.ꢀH. Tan, L.ꢀC. Ding and X.ꢀJ. Wei, Chin. J. Med. Chem., 2001, 11, 259.
10. D. Yang, D. Fokas, J. Li, L. Yu and C. M. Baldino, Synthesis, 2005, 47.
11. Bai, Y.; Lu, J.; Shi, Z.; Yang, B. Synlett 2001, 11, 544–546.
12. Hasegawa, E.; Yoneoka, A.; Suzuki, K.; Kato, T.; Kitazume, T.; Yangi, K. Tetrahedron
1999, 55, 12957–12968.
13. G. A. Molander, K . Ajayi, Org. Lett., 2012, 14, 4242–4245.
14. G. Pranab, M. Amitava, Tetrahedron Lett., 2012, 53, 6483–6488.
15. S. Samuthirarajan, K. Mayilvasagam, Tetrahedron Lett., 2014, 55, 1971–1974.
16. R. Chebolu , D. N. Kommi, D. Kumar, N. Bollineni, A. K. Chakraborti, J. Org. Chem., 2012,
77 , 10158–10167
17. D. Kumar, D. N. Kommi, R. Chebolu, S. K. Garg, R. Kumar, A. K. Chakraborti, RSC Adv.,
2013, 3, 91ꢀ98.
18. M. Chakrabarty, R. Mukherjee, S. Karmakar, and Y. Harigaya, Monatshefte fu¨ r Chemie
2007, 138, 1279–1282.
19. S. Radheshyam, S. Sachin , N. Jayashree , Tetrahedron Lett.; 2013, 54, 6986–6990.
20. Vikash Kumar, G. K. Dipratn, C. Amrita, B. Mainak, Tetrahedron Lett., 2013, 54, 5505–
5509.
21. M. I. Suleman, K. M. Vinod, K. M. Sisir, Tetrahedron Lett., 2013, 54, 579–583.
22. (a) H. Debus, Ann. Chem. Pharm., 1858, 107, 199–208;
23. (a) K .Sivakumar, A .Kathirvel, A .Lalitha. Tetrahedron Lett., 2010, 51, 3018–3021.;(b) S
.Narayana Murthy, B .Madhav, Y. V. D. Nageswar. Tetrahedron Lett., 2010, 51, 5252–
5257; (c) I. M. David, M . Bahramnejad, M. Dabiri. Tetrahedron Lett. 2013, 54, 2591–2594
(d) S .Maity, S. Pathak, A .Pramanik. Tetrahedron Lett., 2013, 54, 2528–2532.; (e) N.P.
Amit, K. A. Devendra, Tetrahedron Lett., 2014, 55, 1835–1838; (f) Z . Zohre and S. Javad,
New J. Chem., 2014, 38, 4555ꢀ4565; (g) S .Javad, A .Zahra, N .Simin. DOI:
10.1016/j.jscs.2012.10.012. (h) P. F. Zhang and Z. C. Z. Chen, Synthesis, 2001, 2075–2077.
24.
S. Tan, X. Li, Y. Guo, Z. Zhang, Nanoscale. 2013, 5, 860ꢀ872.
25. T. Yong, I. Roy, M. T. Swihart, P. N. Prasad, J. Mater. Chem. 2009, 19, 4655ꢀ4672.
26. Z. Zarnegar and J. Safari, New J. Chem., 2014, 38, 4555ꢀ4565.
27. (a) L. BaoꢀLe, Z.Mo, H. HaiꢀChuan, D. Xia and Z. ZhanꢀHui, New J. Chem., 2014, 38,
2435; (b) D. A. Kotadia, U. H. Patel, S. Gandhi and S. S. Soni, RSC Adv., 2014,4, 32826ꢀ
32833.
28. (a) Y. Ding, Y. Wang, L. Zhang, H. Zhang, C. M. Li, Y. Lei, Nanoscale., 2011, 3, 1149ꢀ
1157; (b) O. A. Sadik, A. L. Zhou, S. Kikandi, N. Du, Q. Wang, K. Varner, J. Environ.
Monit., 2009, 11, 1782ꢀ1800; (c) X. D. Wang, O. S. Wolfbeis, J. Robert, Meier, Chem. Soc.
Rev., 2013, 42, 7834ꢀ7869.
29. D. Jariwala, V. K. Sangwan, L. J. Lauhon, T. J. Marks, M. C. Hersam, Chem. Soc. Rev.,
2013, 42, 2824ꢀ2860.
30. J. Liao, Z. Yang, H. Wu, D. Yan, J. Qiu, Z. Song, Y. Yang, D. Zhou and Z. YinH. Kang, Y.
Zhu, X. Yang, J. Shen, C. Chen, C. Li, J. Mater. Chem. C., 2013, 1, 6541–6546.
31. H. Kang, Y. Zhu, X. Yang, J. Shen, C. Chen, C. Li, New J. Chem., 2010, 34, 2166.
32. R. Narayanan, M. A. ElꢀSayed, J. Phys. Chem. B., 2005, 109, 12663ꢀ12676.

Page 23 of 25
RSC Advances
View Article Online
DOI: 10.1039/C5RA13891D
33. (a) J. Zhang, P. X. Ma, Advanced Drug Delivery Reviews., 2013, 65, 1215ꢀ1233. (b) C.
Tudisco,V. Oliveri, M. Cantarella, G. Vecchio, and G. G. Condorelli, Eur. J. Inorg. Chem.,
2012, 5323–5331.
34. B. Aswathy, G. S. Avadhani, S. Suji, G. Sony, Front. Mater. Sci., 2012, 6, 168–175.
35. K. Cai, J. Li, Z. Luo, Y. Hu, Y. Hou and X. Ding, Chem.Commun., 2011, 47, 7719–7721.
36. R. Freeman, T. Finder, L. Bahshi, and I. Willner, Nano Lett., 2009, 9, 2073ꢀ2076.
37. (a) B. Madhav, S. Narayana Murthy, V. Prakash Reddy, K. Rama Rao, Y. V. D. Nageswar,
Tetrahedron Lett.; 2009, 50, 6025–6028; (b) K. Ramesh, K. Karnakar, G. Satish, B. S. P.
Anil Kumar, Y. V. D. Nageswar, Tetrahedron Lett., 2012, 53, 6936–6939; (c) Dipak R.
Patil,Yogesh B. Wagh, Pravin G. Ingole,Kripal Singh and Dipak S. Dalal, New J. Chem.,
2013,37, 3261ꢀ3266; (d) Babak Kaboudin, Ramin Mostafalu and Tsutomu Yokomatsu,
Green Chem., 2013, 15, 2266.
38. K. Tanabe, Mater. Chem. Phys. 1985, 13, 347–364.
39. R. C. Garvie, R. H. Hannink, R. T. Pascoe, Nature, 1975, 258, 703–704.
40. G. D. Wilk, R. M. Wallace, J. M. Anthony, J. Appl. Phys., 2001, 89, 5243ꢀ5275.
41. G. Y. Guo, Y. L. Chen, J. Mater. Chem., 2001, 11, 1283ꢀ1287
42. S. F. Yin, B. Q. Xu, Chem Phys Chem. 2003, 4, 277ꢀ281.
43. A. H. Heuer, L. W. Hobbs, Science and technology of zirconia, American Ceramic Society,
Columbus and Ohio, 1981, vol. 3.
44. M. Inoue, H. Kominami, T. Inui, Appl. Catal. A. 1993, 97, L25–L30.
45. J. Joo, T. Yu, Y. W. Kim, H. M. Park, F. Wu, J. Z. Zhang, T. Hyeon, J. Am. Chem. Soc.
2003, 125, 6553–6557.
46. R. C. Buchanan, S. Pope, J. Electrochem. Soc. 1983, 130, 962ꢀ966.
47. A. Krell, J. Klimke, T. Hutzler, Opt. Mater. 2009, 31, 1144–1150.
48. J. Robertson, Rep. Prog. Phys. 2006, 69, 327–396.
49. G. Liu and Y. Lin, Anal. Chem. 2005, 77, 5894–5901.
50. S .Liu, and M. Y. Han, Chem.–Asian J. 2010, 5, 36–45.
51. J. Lu, J. B. Zang, S. X. Shan, H. Huang, Y. H. Wang, Nano Lett. 2008, 8, 4070–4074.
52. T. Z. Sholklapper, V. Radmilovic, C. P. Jacobson, S. J. Isco, L. C. De Jonghe, Electrochem.
SolidꢀState Lett. 2007, 10, B74–B76.
53. X. Luo, A. Morrin, A. J. Killard, M. R. Smyth, Electroanalysis, 2006, 18, 319–326.
54. S. A. Steiner, Th. F. Baumann, B. C. Bayer, R. Blume, M. A. Worsley, W. J. Moberly
Chan, E. L. Shaw, R. Schlogl, A. John Hart, S. Hofmann, B. L. Wardle, J. Am. Chem. Soc.
2009, 131, 12144–12154.
55. (a) Y. R. Girish, K. S. S. Kumar, H. S. Manasa and S. Shashikanth, J. Chin. Chem. Soc.
2014, 61, 1175ꢀ1179; (b) Y. R. Girish, K. S. S. Kumar, U. Muddegowda, N. K. Lokanath, K.
S. Rangappa, S. Shashikanth, RSC Adv., 2014, 4, 55800–55806; (c) Y. R. Girish, K. R.
Raghavendra, D. Nagaraja, K. S. S. Kumar, S. Shashikanth, Chin. J. Chem. 2015, 33, 181ꢀ
184.
56. L. Bai, A. F. Wyrwalski, C. Machut, P. Roussel, E. Monflier, A. Ponchel, Cryst Eng Comm.,
2013, 15, 2076.
57. K. Ramesh, S. Narayana Murthy, K. Karnakar, Y.V.D. Nageswar, Kukuma Vijayalakhshmi,
Bethala L.A. Prabhavathi Devi, R.B.N. Prasad, Tetrahedron Lett., 2012, 53, 1126ꢀ1129.
58. X.Min , L. Yueꢀdong , Journal of Molecular Catalysis A: Chemical., 2007, 265 , 205–208.
59. S. Saikat Das, H. Parasa , K. Dilip, Tetrahedron Lett., 2008, 49, 2216ꢀ2220.

RSC Advances
Page 24 of 25
View Article Online
DOI: 10.1039/C5RA13891D
60. M. Jafarpour, A. Rezaeifard,M. Ghahramaninezhad and T. Tabibi, New J. Chem., 2013, 37,
2087—2095.
61. (a) V. Srinivas, C. D. Mohan, C. P. Baburajeev, S. Rangappa, S. Jagadish, J. E. Fuchs, A. Y.
Sukhorukov, Chandra, D. J. Mason, K. S. Sharath Kumar, M. Madegowda, A. Bender,
Basappa, K. S. Rangappa, Bioorg. Med. Chem. Lett., 2015, 25, 2931. (b) K. S. Sharath
Kumar, A. Hanumappa, M. Hegde, K. H. Narasimhamurthy, S. C. Raghavan, K. S.
Rangappa, Eur J Med Chem., 2014, 81, 341. (c) K. S. Sharath Kumar, A. Hanumappa, M.
Vetrivel, M. Hegde, Y. R. Girish, T. R. Byregowda, S. Rao, S. C. Raghavan, K. S. Rangappa,
Bioorg. Med. Chem. Lett., 2015, 25, 3616ꢀ3620.
62. P. Bandyopadhya, M. Sathe, S. Ponmariappan, S. Sharma, P. Sharma, A.K. Srivastava, M.
P. Kaushik, Bioorg. Med. Chem. Lett., 2011, 21, 7306–7309.

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ZrO2ꢀβꢀcyclodextrin catalyzed synthesis of 2,4,5ꢀtrisubstituted imidazoles and 1,2ꢀ
disubstituted benzimidazoles under solvent free conditions and evaluation of their
antibacterial study